The central objective of this project is to elucidate the neuronal mechanisms of classical conditioning and sensitization. Furthermore, this project will seek to ascertain if postsynaptic neuromodulatory mechanisms elicited by tail nerve shock during classical conditioning interacts in any way with the activity-dependent associative component of classical conditioning. The neuronal circuitry underlying the behavioral plasticity of the Aplysia siphon withdrawal reflex is well defined and relatively simple. Also, the cellular mechanisms present at the sensorimotor synapse of the Aplysia share many of the same properties of CA3-CA1 synapses in the hippocampus. Both synapses have NMDA-dependent LTP and are influenced by neuromodulators, but the complexity of the mammalian system hinders connecting synaptic changes to the actual learning exhibited by the animal. The neural circuitry underlying classical conditioning in Aplysia is well defined and relatively simplistic, therefore synaptic changes are more readily attributed to the behavioral plasticity of the animal. The proposed experiments will increase our knowledge of synaptic plasticity and provide a basis for understanding the synaptic processes underlying human learning and memory. The increased knowledge may contribute to the understanding of human-memory diseases such as Alzheimer's and other related dementias.